Michael additions of 2-nitropropane

Chiral monoaza-crown ethers containing glucose units have been applied as phase-transfer catalysts in the Michael addition of 2-nitropropane to a chalcone to give the corresponding adduct in up to 90% ee. (Eq. 4.138).202... 

A novel synthesis of 1,2,3-selenadiazoles 338 starts with the Michael addition of 2-nitropropane to a,P-unsaturated ketones 336 under basic conditions <06JHC149>. The resulting adducts are treated with semicarbazide hydrochloride to give semicarbazones 337, which are converted to 1,2,3-selenadiazoles 338 by reaction with selenium dioxide in THF (the choice of the solvent appears to be important in this case). 

Scheme 8.3 Crown ether-induced asymmetric Michael addition of 2-nitropropane to chalcones.

Michael additions of 2-nitropropane to methyl acrylate with soluble, diphenyl-phosphine-functionalized poly(4-tert-butylstyrene) copolymers as nucleophilic catalysts were investigated by Bergbreiter and li [Eq. (9)] [22]. The catalytic reactions were performed in a monophasic system consisting of a mixture of ethanol and heptane at room temperature. After 24 h, a small amount of water was added and phase separation occurred. With this water-induced Hquid/Hquid phase separation, the polymeric catalyst could be recycled and successfully applied again in a catalytic cycle. UV-Vis spectroscopy showed that the catalyst was quantitatively dissolved in the nonpolar, heptane-rich phase. 

Scheme 13.17 Nitroalkane-Michael addition of 2-nitropropane to 2-tyclohexen-l-one catalysed N-terminal primary amino dipeptide 24 in the presence of additives 25 and 26.

Several other high inductions have been reported by using crown ethers as catalysts (Scheme 10.8). The Toke group has used a chiral crown 11 (Chart 10.2), which incorporates a glucose unit, for the addition of 2-nitropropane to a chalcone (Scheme 10.8) [38], Several other effective chiral crowns (12-17, Chart 10.2 and Scheme 10.8) are noted [24e,39-42,48b]. An interesting study of the Michael addition under both solvent-free (0% ee) and liquid-liquid conditions (up to 70% ee) was reported by Diez-Barra and co-workers, who also addressed the question of free -OH quats (28, 58% ee) verses O-benzyl quats (30, 46% ee) [43]. 

The amino acid salt (S)-21 (5-10 mol %) catalyzed the asymmetric Michael addition of nitroalkanes (Scheme 5) [24,25]. Substituted nitromethanes exhibited higher enantiomeric excesses, and addition of 2-nitropropane to cyclohep-tenone 20 gave (R)-27 in 73% ee. In case of primary nitroalkane, two diastere-omers of 28 were formed in comparable amounts, both of which possessed the... 

For carbon nucleophiles sequential addition of 2-potassio-2-nitropropane and oxygen to 4-arylidene-2-phenyl-5(47/)-oxazolones 623 has been reported (Scheme 7.200). The process involves a Michael reaction of the 2-nitropropane anion followed by reaction with molecular oxygen and elimination of nitrous acid to yield 2-aryl butenoic acid imides 626. 

Further applications of the chiral ammonium bifluoride-catalyzed enantioselective Michael addition of silyl nitronates has been shown in the reactions with nitroalkenes as a Michael acceptor (Scheme 9.17). These studies were started by examining the reaction of nitropropane-derived silyl nitronate 23b with P-nitrostyrene, using the chiral quaternary ammonium bifluoride (R,.R)-6d. When P-nitrostyrene was treated with 23b (1.2 equiv.) in the presence of (K,f )-6d (2mol%) in THF at — 78 °C, the... 

We found that Michael addition of nitroalkanes had limited success with nitromethane owing to its nitroaldol reaction with the products formed from methyl vinyl ketone and cyclohexenone, for example. (It may be noted in this regard that although the product obtained in the reaction of methyl vinyl ketone with nitromethane was achieved in 78% yield [127], a recent report [128] described a 98 % yield by employing the less basic catalyst TBD at a higher temperature 0°C). However, 2-nitropropane and nitrocyclohexane were much better candidates for pro-azaphosphatrane-catalyzed reactions for which DBU and TMG typically require longer reaction times and afford only poor to modest product yields [127]. 

Tanikaga and coworkers have reported the addition of nitroalkane anions to a-halo-a,P-unsaturated sulfoxides [72]. Further development of this work led to the use of nitroalkanes as alkyl group equivalents in conjugate addition to a,P-unsaturated sulfoxides [73-75]. Primary or secondary nitroalkanes such as 2-nitropropane (77), with DBU as a non-nucleophilic base, add to a,P-unsaturated sulfoxides including phenyl vinyl sulfoxide (26) to give products such as (78), which can be denitrated to yield (79) (Scheme 5.25). The Michael addition of nitroalkanes, and of diethyl N-acetylaminomalonate, to racemic phenyl vinyl sulfoxide using solid-liquid phase-transfer catalysis in the absence of solvent has also been accomplished [76]. 

Du and coworkers have developed a stereoselective direct Michael addition of nitroalkanes to nitroalkenes catalyzed by quinine-derived dimeric squaramide 21 [93]. This transformation provided facile access to 1,3-dinitro compounds in high diastereo- and enantioselectivities starting from aryl-substituted nitroalkenes (Scheme 10.18). However, the use of an aliphatic nitroalkene as Michael acceptor resulted in a low yield and diminished enantioselectivity. While nitroethane and 1-nitropropane are excellent substrates, branched 2-nitropropane did not undergo the Michael addition reaction. The authors also noted that slightly reduced dias-... 

Regioselective Michael additions of nitroalkanes to levoglucosenone under cadiodic electrolysis conditions have been reported and can be illustrated by the use of 2-nitropropane to give derivative 26. ... 

By contrast, L-phenylalanine methyl ester does not react with BENA generated from 1-nitropropane (R =H) due apparently to low nucleophilicity of the amino group. However, the N, C -coupling reaction of the ester of this amino acid with another internal BENA (R = CC>2Me) proceeds rather readily but is characterized by extremely low diastereoselectivity. Probably, the last N,C-coupling does not occur via an intermediate a-nitroso alkene but by a classical Michael addition to BENA MeCH=C(C02Me)N(05i )2 as to Michael substrate. 

A The product A contains all the atoms of the precursor molecules and hence a simple addition has taken place. 2-Nitropropane has an acidic hydrogen and hence it can form a carbanion. Methyl acrylate is an unsaturated ester and can act as a Michael acceptor for a carbanion. The reaction may therefore be formulated as ... 

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